Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation
Ultraviolet (UV) irradiation of HeLa cells triggers an apoptotic response mediated by mitochondria. Biochemical analysis of this response revealed that the elimination of cytosolic inhibitors is required for mitochondrial release of cytochrome c and subsequent caspase activation. These inhibitors we...
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| Veröffentlicht in: | Genes & development 2003-06, Vol.17 (12), p.1475-1486 |
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| creator | Nijhawan, Deepak Fang, Min Traer, Elie Zhong, Qing Gao, Wenhua Du, Fenghe Wang, Xiaodong |
| description | Ultraviolet (UV) irradiation of HeLa cells triggers an apoptotic response mediated by mitochondria. Biochemical analysis of this response revealed that the elimination of cytosolic inhibitors is required for mitochondrial release of cytochrome c and subsequent caspase activation. These inhibitors were found to be Mcl-1 and Bcl-xL, two antiapoptotic members of the Bcl-2 family. Following UV treatment, Mcl-1 protein synthesis is blocked, the existing pool of Mcl-1 protein is rapidly degraded by the proteasome, and cytosolic Bcl-xL translocates to the mitochondria. These events are sequential; the elimination of Mcl-1 is required for the translocation of Bcl-xL. The disappearance of Mcl-1 is also required for other mitochondrial apoptotic events including Bax translocation, cytochrome c release, and caspase activation. |
| doi_str_mv | 10.1101/gad.1093903 |
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Biochemical analysis of this response revealed that the elimination of cytosolic inhibitors is required for mitochondrial release of cytochrome c and subsequent caspase activation. These inhibitors were found to be Mcl-1 and Bcl-xL, two antiapoptotic members of the Bcl-2 family. Following UV treatment, Mcl-1 protein synthesis is blocked, the existing pool of Mcl-1 protein is rapidly degraded by the proteasome, and cytosolic Bcl-xL translocates to the mitochondria. These events are sequential; the elimination of Mcl-1 is required for the translocation of Bcl-xL. The disappearance of Mcl-1 is also required for other mitochondrial apoptotic events including Bax translocation, cytochrome c release, and caspase activation.</description><identifier>ISSN: 0890-9369</identifier><identifier>EISSN: 1549-5477</identifier><identifier>DOI: 10.1101/gad.1093903</identifier><identifier>PMID: 12783855</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Amino Acid Chloromethyl Ketones - pharmacology ; Apoptosis - physiology ; Apoptosis - radiation effects ; bcl-X Protein ; Caspase Inhibitors ; Caspases - metabolism ; Cysteine Endopeptidases - metabolism ; Cysteine Proteinase Inhibitors - pharmacology ; Cytochrome c Group - metabolism ; Cytochrome c Group - radiation effects ; Cytosol - metabolism ; HeLa Cells - radiation effects ; Humans ; Leupeptins - pharmacology ; Mitochondria - metabolism ; Mitochondria - radiation effects ; Multienzyme Complexes - antagonists & inhibitors ; Multienzyme Complexes - metabolism ; Myeloid Cell Leukemia Sequence 1 Protein ; Neoplasm Proteins - genetics ; Neoplasm Proteins - isolation & purification ; Neoplasm Proteins - metabolism ; Proteasome Endopeptidase Complex ; Protein Transport - radiation effects ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Proto-Oncogene Proteins c-bcl-2 - isolation & purification ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Research Papers ; Signal Transduction ; Ultraviolet Rays - adverse effects</subject><ispartof>Genes & development, 2003-06, Vol.17 (12), p.1475-1486</ispartof><rights>Copyright © 2003, Cold Spring Harbor Laboratory Press 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-ba65aa8e9618e9245f3e66675753cfde30e7672827f46a9a6b0929b0cb65ab523</citedby><cites>FETCH-LOGICAL-c473t-ba65aa8e9618e9245f3e66675753cfde30e7672827f46a9a6b0929b0cb65ab523</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC196078/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC196078/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12783855$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nijhawan, Deepak</creatorcontrib><creatorcontrib>Fang, Min</creatorcontrib><creatorcontrib>Traer, Elie</creatorcontrib><creatorcontrib>Zhong, Qing</creatorcontrib><creatorcontrib>Gao, Wenhua</creatorcontrib><creatorcontrib>Du, Fenghe</creatorcontrib><creatorcontrib>Wang, Xiaodong</creatorcontrib><title>Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>Ultraviolet (UV) irradiation of HeLa cells triggers an apoptotic response mediated by mitochondria. Biochemical analysis of this response revealed that the elimination of cytosolic inhibitors is required for mitochondrial release of cytochrome c and subsequent caspase activation. These inhibitors were found to be Mcl-1 and Bcl-xL, two antiapoptotic members of the Bcl-2 family. Following UV treatment, Mcl-1 protein synthesis is blocked, the existing pool of Mcl-1 protein is rapidly degraded by the proteasome, and cytosolic Bcl-xL translocates to the mitochondria. These events are sequential; the elimination of Mcl-1 is required for the translocation of Bcl-xL. The disappearance of Mcl-1 is also required for other mitochondrial apoptotic events including Bax translocation, cytochrome c release, and caspase activation.</description><subject>Amino Acid Chloromethyl Ketones - pharmacology</subject><subject>Apoptosis - physiology</subject><subject>Apoptosis - radiation effects</subject><subject>bcl-X Protein</subject><subject>Caspase Inhibitors</subject><subject>Caspases - metabolism</subject><subject>Cysteine Endopeptidases - metabolism</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>Cytochrome c Group - metabolism</subject><subject>Cytochrome c Group - radiation effects</subject><subject>Cytosol - metabolism</subject><subject>HeLa Cells - radiation effects</subject><subject>Humans</subject><subject>Leupeptins - pharmacology</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - radiation effects</subject><subject>Multienzyme Complexes - antagonists & inhibitors</subject><subject>Multienzyme Complexes - metabolism</subject><subject>Myeloid Cell Leukemia Sequence 1 Protein</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - isolation & purification</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Proteasome Endopeptidase Complex</subject><subject>Protein Transport - radiation effects</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - isolation & purification</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Research Papers</subject><subject>Signal Transduction</subject><subject>Ultraviolet Rays - adverse effects</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkb1PwzAQxS0EoqUwsSNPLCjFjmM7HhhQVT6kIhaYLSdxWiMnbm2niP-eVI0KTCx3w_3e09M9AC4xmmKM8O1SVVOMBBGIHIExpplIaMb5MRijXKBEECZG4CyED4QQQ4ydghFOeU5ySsegmFvTmFZF41roavhS2gRDE6DXm854XcHaeRhXGprWRHPg1Nqtows9WDtr3adpl7Cz0autcVZHaLxX1R4_Bye1skFfDHsC3h_mb7OnZPH6-Dy7XyRlxklMCsWoUrkWDPcjzWhNNGOMU05JWVeaIM0ZT_OU1xlTQrECiVQUqCx6XUFTMgF3e991VzS6KnXbx7Fy7U2j_Jd0ysi_l9as5NJtJRYM9f-YgOtB792m0yHKxoRSW6ta7bogOSF5lhH2L4jz3i1Du0Q3e7D0LgSv60MYjOSuO9l3J4fuevrqd_4fdiiLfAOth5cr</recordid><startdate>20030615</startdate><enddate>20030615</enddate><creator>Nijhawan, Deepak</creator><creator>Fang, Min</creator><creator>Traer, Elie</creator><creator>Zhong, Qing</creator><creator>Gao, Wenhua</creator><creator>Du, Fenghe</creator><creator>Wang, Xiaodong</creator><general>Cold Spring Harbor Laboratory Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20030615</creationdate><title>Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation</title><author>Nijhawan, Deepak ; 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Biochemical analysis of this response revealed that the elimination of cytosolic inhibitors is required for mitochondrial release of cytochrome c and subsequent caspase activation. These inhibitors were found to be Mcl-1 and Bcl-xL, two antiapoptotic members of the Bcl-2 family. Following UV treatment, Mcl-1 protein synthesis is blocked, the existing pool of Mcl-1 protein is rapidly degraded by the proteasome, and cytosolic Bcl-xL translocates to the mitochondria. These events are sequential; the elimination of Mcl-1 is required for the translocation of Bcl-xL. The disappearance of Mcl-1 is also required for other mitochondrial apoptotic events including Bax translocation, cytochrome c release, and caspase activation.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>12783855</pmid><doi>10.1101/gad.1093903</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Chloromethyl Ketones - pharmacology Apoptosis - physiology Apoptosis - radiation effects bcl-X Protein Caspase Inhibitors Caspases - metabolism Cysteine Endopeptidases - metabolism Cysteine Proteinase Inhibitors - pharmacology Cytochrome c Group - metabolism Cytochrome c Group - radiation effects Cytosol - metabolism HeLa Cells - radiation effects Humans Leupeptins - pharmacology Mitochondria - metabolism Mitochondria - radiation effects Multienzyme Complexes - antagonists & inhibitors Multienzyme Complexes - metabolism Myeloid Cell Leukemia Sequence 1 Protein Neoplasm Proteins - genetics Neoplasm Proteins - isolation & purification Neoplasm Proteins - metabolism Proteasome Endopeptidase Complex Protein Transport - radiation effects Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - isolation & purification Proto-Oncogene Proteins c-bcl-2 - metabolism Research Papers Signal Transduction Ultraviolet Rays - adverse effects |
| title | Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation |
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